Phencyclidine (PCP) is a widely self-administered psychedelic drug of abuse, and the treatment and management of patients suffering from acute and chronic PCP intoxication poses a major health problem. In low doses, PCP causes hallucination, ataxia, catatonia, nystagmus, analgesia and anesthesia. At high doses, PCP results in long periods of stupor, seizures, confusion and psychosis characterized as schizophreniform. Before the mechanisms underlying PCP intoxication and the induction of bizarre bahavior can be understood, it is essential that the biodisposition of PCP be studied throughout the intact animal, avoiding the use of postmortem tissues which seriously limits interpretation of tissue distribution data. Previous studies on the disposition and metabolism of PCP in laboratory animals, often contradictory, have been confined to use of in vitro preparations of synaptic membranes from rat brain, homogenates of dissected CNS and peripheral tissues or in vitro incubated frozen slide-mounted sections of dissected rat CNS. The nonphysiological conditions under which the majority of this information has been obtained, in vitro, raises serious questions on the validity of correlating the resulting data on distribution and metabolism of PCP with normal physiological processes involving an intact vascular drug delivery system, a functional choroid plexus and blood-brain barrier in the CNS and respiring neurons and neuroglia. The present study employs the WBAR in vivo method which provides for an instantaneous arrest of drug migration from sites of drug sequestration and yields high-resolution information on unaltered histologic patterns of drug uptake. The specific aims of the present investigation are: (1) to study, by WBAR, the in vivo distribution of (3H)-PCP in mice throughout the whole animal after receiving single and multiple PCP treatments; (2) to evaluate, by WBAR, the specificity of (3H)-PCP binding in CNS and peripheral tissue sites by displacement studies of (3H)-PCP in adult mice and in fetuses of pregnant mice injected with effective displacers; (3) to quantify the radioactivity in completed autoradiograms by the method of computer-assisted videodensitometry; (4) to quantify parent PCP and its major metabolites in cryosections and dissected tissues employing thin layer chromatography and liquid scintillation spectrometry.